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Congress, when considering how to determine risk significance, decided that neither the already overburdened FDA nor the typically small device companies needed the additional bureaucracy. Congress ultimately established that if an IRB considered a device to be non-significant risk then that device would automatically be considered to have an IDE. The question was how to determine if the device was non-significant.

The following is the simplest possible primer on devices. Many nuances and technicalities are lost in the simplification. The FDA Information Sheets are required reading.

CRITICAL: Regardless of their decision regarding significant risk, under the regulations an IRB must still also make decisions about risk/benefit, risk minimization, and the risk statement on the consent document. These are separate determinations.

AND presents a potential for serious risk to the health, safety, or welfare of a subject;

2. is purported or represented to be for a use in supporting or sustaining human life

AND presents a potential for serious risk to the health, safety, or welfare of a subject;

3. is for a use of substantial importance in diagnosing, curing, mitigating or treating disease, or otherwise preventing impairment of human health

AND presents a potential for serious risk to the health, safety, or welfare of a subject; or

4. otherwise presents a potential for serious risk to the health, safety, or welfare of a subject.”

A shortened definition could say that a significant risk device is an investigational device that presents a potential for serious risk to the health, safety, or welfare of a subject.

HOW IS THE DEFINITION INTERPRETED?

The first paragraph of FDA’s September 1998 guidance says, The Investigational Device Exemption (IDE) regulations… describe two types of device studies….. This simple change from “device” to “device study” is critical. It derives from 812.2(b)(ii); an IRB approves a study after presentation of a brief explanation of why the device is not a significant risk device. FDA believes there to be one decision: approval after presentation. It could be that there are two IRB decisions:

(1) Is the device, as it is to be used in the context of the protocol, an SR device and

(2) Can the study be approved?

IRB POLICIES

E&I’s policy is in the Guidance Section / E&I NSR Policy

WHAT IS THE EFFECT OF THE IRB’s DECISION?

There is one direct effect of the IRB’s decision. A decision that the device (or device study) is SR means that the FDA must become involved for the study to proceed. A decision of NSR means that the study can begin immediately without involvement of FDA.

HOW DOES AN IRB DECIDE?

At the time of IRB submission the sponsor should have decided on a course of action. If the sponsor believes the device (or device study) to be SR, the IDE application should be obtained or already under review. If the sponsor believes the device (or device study) to be NSR, it should make that contention to the IRB.

1. Make the claim

The sponsor should be clear that they are contending that the device (or device study) is NSR.

2. Support the claim (Do not simply repeat the definition)

Identify all of the potential risks. Describe whether they are risks of the clinical care, of a study related procedure or are of the investigational device. Evaluate each one in terms of severity and frequency. If there is a difference in the potential for harm between something used outside research and used in a study (where, perhaps, there is closer observation), make that difference clear.

3. Describe any steps being taken to minimize the risks.

If something could cause a life-threatening infection if left untreated but is being monitored the risk, in that context, is lowered.

CAN THE IRB BE WRONG? IF SO, WHAT HAPPENS?

No, the determination of the IRB is their opinion and cannot be wrong. The IRB can, however, make a reasonable and rationale and documented decision that is not acceptable to the FDA.

The IRB, as a surrogate for FDA, has made a good faith decision based on available information. The sponsor has elected to proceed without double-checking with the FDA. The sponsor is taking an economic gamble.